Michael M. Shen, PhD
During the past twenty-three years, my laboratory has investigated the molecular mechanisms of mammalian development and cancer using in vivoanalyses of genetically-engineered mouse models. After establishing my lab at Rutgers-Robert Wood Johnson Medical School, my group focused on functional analyses of the signaling pathway for the TGF-beta ligand Nodal, and elucidation of the multiple mechanisms of its regulation during mouse embryogenesis.
Since moving to Columbia University Medical School in 2007, our studies have expanded significantly to encompass analyses of prostate epithelial progenitor cells and their roles in organogenesis and tissue regeneration, focusing on the role of the Nkx3.1 transcriptional regulator as well as analysis of cell types of origin for prostate cancer. These studies have led to the identification of a luminal epithelial stem cell as well as support for a luminal cell of origin for prostate cancer, and most recently to the establishment of an organoid culture system for mouse and human prostate epithelium. Our work has also incorporated bioinformatic and computational systems approaches in studies ranging from analyses of extraembryonic endoderm stem cell differentiation to the investigation of prostate epithelial lineage specification. Ongoing projects include systems analyses of embryonic stem cell pluripotency, investigation of mechanisms of prostate epithelial lineage specification and cell-type differentiation, and generation of novel mouse models of advanced prostate cancer. Most recently, the scope of our projects has expanded to molecular studies of bladder cancer evolution and drug response through the analysis of patient-derived bladder tumor organoids.
Wang, X., Kruithof-de Julio, M., Economides, K. D., Walker, D., Yu, H., Halili, M. V., Hu, Y.-P., Price, S. M., Abate-Shen, C., and Shen, M. M. (2009). A luminal epithelial stem cell that is a cell of origin for prostate cancer. Nature 461: 495-500. PMCID: PMC2800362.
Chu, J., and Shen, M. M. (2010). Functional redundancy of EGF-CFC genes in epiblast and extraembryonic patterning during early mouse embryogenesis. Dev. Biol. 342: 63-73. PMCID: PMC2866749.
Shen, M. M., and Abate-Shen, C. (2010). Molecular genetics of prostate cancer: new prospects for old challenges. Genes Dev. 24: 1967-2000. PMCID: PMC2939361.
Kruithof-de Julio, M., Alvarez, M. J., Galli, A., Chu, J., Price, S. M., Califano, A., and Shen, M. M. (2011). Regulation of extraembryonic endoderm stem cell differentiation by Nodal and Cripto signaling. Development 138: 3885-3895. PMCID: PMC3160087.
Wang, Z. A., Mitrofanova, A., Bergren, S. K., Abate-Shen, C., Cardiff, R. D., Califano, A., and Shen, M. M. (2013). Lineage analysis of basal epithelial cells reveals their unexpected plasticity and supports a cell of origin model for prostate cancer heterogeneity. Nat. Cell Biol. 15: 274-283. PMCID: PMC3743266.
Chua, C. W., Shibata, M., Lei, M., Toivanen, R., Barlow, L. J., Bergren, S. K., Badani, K. K., McKiernan, J. M., Benson, M. C., Hibshoosh, H., and Shen, M. M. (2014). Single luminal epithelial progenitors can generate prostate organoids in culture. Nat. Cell Biol. 16: 951-961. PMCID: PMC4183706.
Wang, Z. A., Toivanen, R., Bergren, S. K., Chambon, P., and Shen, M. M. (2014). Luminal cells are favored as the cell of origin for prostate cancer. Cell Rep. 8: 1339-1346. PMCID: PMC4163115.
Toivanen, R., Mohan, A., and Shen, M. M. (2016). Basal progenitors contribute to repair of the prostate epithelium following induced luminal anoikis. Stem Cell Rep. 6: 660-667. PMCID: PMC4939748.
Zou, M., Toivanen, R., Mitrofanova, A., Floc’h, N., Hayati, S., Sun, Y., Le Magnen, C., Chester, D., Mostaghel, E. A., Califano, A., Rubin, M. A., Shen, M. M., and Abate-Shen, C. (2017). Transdifferentiation as a mechanism of treatment resistance in a mouse model of castration-resistant prostate cancer. Cancer Discov. 7: 736-749. PMCID: PMC5501744.
Toivanen, R., and Shen, M. M. (2017). Prostate organogenesis: tissue induction, hormonal regulation and cell type specification. Development 144: 1382-1398. PMCID: PMC5399670.
Talos, F., Mitrofanova, A., Bergren, S. K., Califano, A., and Shen, M. M. (2017). A computational systems approach identifies synergistic specification genes that facilitate lineage conversion to prostate tissue. Nat. Comm. 8: 14662. PMCID: PMC5413950.
Chua, C. W., Epsi, N. J., Leung, E. Y., Xuan, S., Lei, M., Li, B. I., Bergren, S. K., Hibshoosh, H., Mitrofanova, A., and Shen, M. M.(2018). Differential requirements of androgen receptor in luminal progenitors during prostate regeneration and tumor initiation. eLife 7: e28768. PMCID: PMC5807048.
Lee, S. H., Hu, W., Matulay, J. T., Silva, M. V., Owczarek, T. B., Kim, K., Chua, C. W., Barlow, L. J., Kandoth, C., Williams, A. B., Bergren, S. K., Pietzak, E. J., Anderson, C. B., Benson, M. C., Coleman, J. A., Taylor, B. S., Abate-Shen, C., McKiernan, J. M., Al-Ahmadie, H., Solit, D. B., and Shen, M. M.(2018) Tumor evolution and drug response in patient-derived organoid models of bladder cancer. Cell 173: 515-528. PMCID: PMC5890941.